AIM2 Mediates Inflammation-Associated Renal Damage in Hepatitis B Virus-Associated Glomerulonephritis by Regulating Caspase-1, IL-1β, and IL-18

Abstract

Background & Aims. AIM2 plays an important role in innate immunity, but its role in regulating the immune response to hepatitis B virus (HBV) is unknown. We hypothesized that AIM2 expression is positively correlated with HBV-mediated inflammation in patients with HBV-associated glomerulonephritis (HBV-GN), potentiating inflammation and leading to renal damage. We therefore analyzed the expression of AIM2 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection and HBV status. Methods. Seventy-nine patients with chronic nephritis (CN) were included: 54 with HBV-GN and 24 with chronic glomerulonephritis (CGN). Expression of AIM2, caspase-1, and IL-1β was detected by immunohistochemistry in renal biopsies from each patient. Following siRNA-mediated knockdown of AIM2 in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cells, expression of caspase-1, IL-1β, and IL-18 was detected by qRT-PCR and Western blot. Results. AIM2 expression in HBV-GN biopsies (81.4%) was significantly higher than in CGN (4.0%) and positively correlated with caspase-1 and IL-1β expression in HBV-GN. In vitro, AIM2 knockdown reduced caspase-1, IL-1β, and IL-18 expression in HBV-infected and HBV-uninfected HGM cells. Conclusion. AIM2 elevation during HBV infection or replication may contribute to inflammatory damage, thus providing a putative therapeutic target for HBV-GN.

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

“…This process has not been studied in vivo so far and whether it benefits to host or pathogen needs to be investigated. AIM2 was also reported to promote inflammation‐mediated renal damage in patients with Hepatitis B virus‐associated glomerulonephritis (HBV‐GN) . AIM2 was detected in glomerular endothelial and mesangial cells of patients with HBV‐GN and AIM2 silencing in human mesangial cells infected with HBV led to decreased expression of IL‐1β and IL‐18 .…”

Inflammasome control of viral infection

“…Expression of AIM2, IL-1β and IL-18 in hepatitis B virus (HBV) infected human PBMCs correlates with viral load, and AIM2 expression is lower in chronic as compared to acute cases [26]. AIM2 expression also correlates with renal damage during HBV infection, possibly indicating that AIM2 enhances immunopathology during HBV infection [27,28], but a definitive role remains to be determined.…”

DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

“…Upregulation of AIM2 strongly correlates with HBV load and enhanced inflammation in CHBV patients [17, 18, 95]. Similar AIM2 effects were observed in patients with HBV-induced glomerulonephritis, suggesting an important central role of AIM2 in contributing to inflammatory damage and severe disease progression [19]. Downregulation of caspase 1 and ACS was reported in the peripheral blood mononuclear cells of CHBV patients compared to their normal counterparts, suggesting a mechanism in which activation of pro-IL-1 β and pro-IL-18 occurs in subsequent to HBV infection [96].…”